So i'm looking to buy a really nice set of headphones. I've done plenty of reading recently on whats out there but i'm no expert so i'm just looking for a little more insight from any of you that have some knowledge or experience with high end headphones.

I'm willing to spend up to about 400 bucks so price isn't really a big issue. I'm leaning toward Bowers and Wilkins p5's. There are a lot of others that intrigue me though.

I have a pair of Sennheiser PXC 350s... it's been 3 or 4 years, so you can obviously find newer Sennheisers out there, but I really enjoy them. I love flipping the noise-canceling switch when I'm in a plane, and they sound great.

That said, I tried a pair of Bose noise-canceling headphones a year or two ago while I was sitting with someone in an airport, and they definitely did a better job of reducing background noise. If that's a big concern, you should definitely try them.

I read somewhere that those headphones are "too bright" or simply put the treble is super high. Also heard they aren't incredibly comfortable for extended use. What do you think?

I actually find them to be quite comfortable. Very light weight. No issues with the sound whatsoever. The only thing is that it doesn't have a remote so when I'm on the go I need to manually skip songs/adjust volume so I just keep then at the office. They may have updated them since I purchased mine a couple years back.
I use my Marshall Majors when walking around only for the remote and mic. They were cheaper ($100) with decent sound but not comfortable at all. Need to take them off after a little while.
I also have the Beats Tour earphones. I got these as a wedding party gift. Killer sound but again, no remote to skip songs/adjust volume which is a big negative for me.
I would spend some time testing them all out.

I was actually wondering, with higher quality headphones, how much of an affect on the listening experience does the Audio file itself have? For instance if I have a 264/320kbps MP3 file, would that suffice or would it show with higher quality headphones.

I read somewhere that those headphones are "too bright" or simply put the treble is super high. Also heard they aren't incredibly comfortable for extended use. What do you think?

I did a lot of looking around before buying a pair of the 325i's and have zero regrets. They sound great and are comfortable. I paid $299 a few years ago for mine and they're worth every penny. Made in the USA, too.